Immunoglobulin G is known to enhance the rate and extent of alternative complement pathway activation on a variety of targets, and to facilitate complement-mediated destruction of some bacteria and virus-infected cells. We have shown the C3b residues covalently deposited on IgG are relatively protected from the actions of serum factors H and I, and hence have enhanced capacity to sustain alternative pathway activation. Recent studies have been directed at the interaction of covalent C3b-IgG complexes with phagocytic cells. Such heterodimeric complexes have been shown to interact readily with human polymorphonuclear leukocyte CR1 and Fc receptors under conditions which mimic the plasma environment and preclude binding of the individual proteins (C3b and IgG). Heterodimer binding has been shown to be dependent on both complement and immunoglobulin receptors and to result in a physiologic response by the cell: ingestion of the bound complexes. In additional studies, we have shown that C3b-IgG heterodimeric complexes are highly efficient opsonins and elicit greater phagocytic activity by both polymorphonuclear leukocytes and mononuclear phagocytes than opsonization of target particles by equal numbers of C3b and IgG residues randomly deposited. Parallel studies have been undertaken to characterize the effect of CR1 crosslinking on phagocyte function. We have shown that CR1 crosslinking elicits receptor internalization, with some degree of subsequent recycling, and in addition primes at least mononuclear phagocytes for enhanced IgG-dependent phagocytosis. Future directions will include: 1) studies of mechanisms of transmembrane signal generation by C3b-IgG complexes, 2) further exploration of phagocyte "priming" for various host defense functions and 3) potential pathogenetic consequences of C3b-IgG interactions in disease states.